Document Detail

Postnatal PPARdelta activation and myostatin inhibition exert distinct yet complimentary effects on the metabolic profile of obese insulin-resistant mice.
MedLine Citation:
PMID:  20593012     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARdelta agonist and endurance training mimetic (GW501516) and a myostatin antibody and resistance training mimetic (PF-879) on metabolic and performance outcomes in obese insulin resistant mice.
METHODOLOGY/PRINCIPAL FINDINGS: Male ob/ob mice were treated for 6 weeks with vehicle, GW501516, PF-879, or GW501516 in combination with PF-879. The effects of the interventions on body composition, glucose homeostasis, glucose tolerance, energy expenditure, exercise capacity and metabolic gene expression were compared at the end of study. GW501516 attenuated body weight and fat mass accumulation and increased the expression of genes of oxidative metabolism. In contrast, PF-879 increased body weight by driving muscle growth and altered the expression of genes involved in insulin signaling and glucose metabolism. Despite their differences, both interventions alone improved glucose homeostasis. Moreover, GW501516 more effectively improved serum lipids, and PF-879 uniquely increased energy expenditure, exercise capacity and adiponectin levels. When combined the robust effects of GW501516 and/or PF-879 on body weight, adiposity, muscle mass, glycemia, serum lipids, energy expenditure and exercise capacity were highly conserved.
CONCLUSIONS/SIGNIFICANCE: The data, for the first time, demonstrate postnatal inhibition of myostatin not only promotes gains in muscle mass similar to resistance training,but improves metabolic homeostasis. In several instances, these effects were either distinct from or complimentary to those of GW501516. The data further suggest that strategies to increase muscle mass, and not necessarily oxidative capacity, may effectively counter insulin resistance and T2DM.
Barbara L Bernardo; Timothy S Wachtmann; Patricia G Cosgrove; Max Kuhn; Alan C Opsahl; Kyle M Judkins; Thomas B Freeman; John R Hadcock; Nathan K LeBrasseur
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-25
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-01     Completed Date:  2010-09-01     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e11307     Citation Subset:  IM    
Cardiovascular, Metabolic and Endocrine Diseases, Pfizer Global Research and Development, Groton, Connecticut, United States of America.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adiponectin / metabolism
Antibodies, Monoclonal / immunology
Body Composition
Citrate (si)-Synthase / metabolism
Energy Metabolism*
Gene Expression Regulation
Glucose / metabolism
Insulin / metabolism
Insulin Resistance*
Lipid Metabolism
Mice, Inbred C57BL
Myostatin / antagonists & inhibitors*,  immunology
Obesity / metabolism*
PPAR delta / agonists*
Physical Conditioning, Animal
Polymerase Chain Reaction
Triglycerides / metabolism
Reg. No./Substance:
0/Adiponectin; 0/Antibodies, Monoclonal; 0/Insulin; 0/Myostatin; 0/PPAR delta; 0/Triglycerides; 50-99-7/Glucose; EC (si)-Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Functional and behavioral restoration of vision by gene therapy in the guanylate cyclase-1 (GC1) kno...
Next Document:  A major histocompatibility Class I locus contributes to multiple sclerosis susceptibility independen...